Optical resolution by chromatography has conventionally been attracting attention remarkably in various fields including analytical chemistry, organic chemistry, medicine, and pharmacy, and a large number of chiral stationary phases have been reported in the world. In particular, for example, an ester derivative or carbamate derivative obtained by chemically modifying cellulose or amylose as an optically active polymer serves as a chiral stationary phase having a high optical resolution, and a filler for chromatography using this derivative has been known to the public. A filler for chromatography using this polymer compound derivative is used in a state of being carried by a carrier such as silica gel for the purposes of, for example, increasing the ratio at which a column is filled with the filler, and improving the ease of handling and mechanical strength of the filler.
For example, Patent Document 1 describes a filler for chromatography obtained by causing a carrier such as silica to carry a cellulose derivative containing an aromatic ring. In addition, Patent Document 2 describes a filler for chromatography obtained by causing a carrier such as silica to carry a carbamate derivative of a polysaccharide such as amylose.
However, the above conventional fillers for chromatography each using a polymer compound such as a polysaccharide derivative are each such that the polymer compound merely is adsorbed physically to the carrier so as to be carried. Accordingly, in some elution solvents, the polymer compound dissolves in any one of the elution solvents, with the result that each of the fillers becomes unusable in some cases.
In particular, the fractionation of a large amount of optical isomers requires the dissolution of a high concentration of a raw material before separation in an elution solvent. An elution solvent capable of meeting the requirement has been perceived as a problem because a polymer compound such as a polysaccharide derivative generally shows a high solubility in the elution solvent.
In addition, the polymer compound such as a polysaccharide derivative has so small a mechanical strength that the following problem arises, particularly when the polymer compound is used for HPLC, the polymer compound cannot withstand a pressure at the time of using HPLC.
In order that those problems may be prevented, attempts have been made to bond the polymer compound, such as a polysaccharide derivative, chemically to the surface of a carrier to improve the mechanical strength of the polymer compound as well as to prevent the elution of the polymer compound due to an elution solvent.
For example, Patent Document 3 discloses a filler for chromatography obtained by chemically bonding an optically active polymer compound to silica gel. However, in the above filler for chromatography described in Patent Document 3, only a trace amount of the polymer compound chemically bonded to the surface of a carrier such as silica contributes to optical resolution, so the filler is susceptible to improvement so that the filler may achieve an additionally high separation ability. In addition, the above filler described in Patent Document 3 cannot be produced efficiently because the filler requires a large number of steps for bonding the polymer compound and silica gel.
In addition, Patent Document 4 describes the following method: a polymerizable group is introduced into each of a polysaccharide and a carrier, and the polysaccharide is chemically bonded to the carrier by the copolymerization of the polysaccharide and the carrier in the presence of a compound having any other polymerizable unsaturated group. However, a reaction time required for the radical polymerization is as long as twenty hours, and the number of steps increases when the polymerizable group is introduced into the carrier. Accordingly, the production of a filler cannot be efficiently performed by the method, so the method is susceptible to improvement.
Meanwhile, Non-patent Document 1 discloses a cellulose derivative to be used in the separation of optical isomers, and describes a method involving the use of a silane coupling agent as a spacer for chemically bonding the cellulose derivative onto a silica matrix. However, NMR analysis has shown that the cellulose derivative obtained by the method shows no signal derived from silica, so it has been estimated that substantially no silane coupling agent is introduced into the cellulose derivative.    Patent Document 1: JP 60-142930 A    Patent Document 2: JP 60-226831A    Patent Document 3: JP 60-196663 A    Patent Document 4: JP 2002-148247 A    Non Patent Document 1: J. Chromatogr. A, 1010 (2003)185-194